Sorbonne Université, INSERM, CNRS, Institut de la Vision, F-75012, Paris, France.
Sorbonne Université, INSERM, CNRS, Institut de la Vision, F-75012, Paris, France; Department of Ophthalmology, The University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, United States; CHNO des Quinze-Vingts, INSERM-DGOS CIC 1423, F-75012, Paris, France; Fondation Ophtalmologique Rothschild, F-75019, Paris, France.
Prog Retin Eye Res. 2022 Jan;86:100975. doi: 10.1016/j.preteyeres.2021.100975. Epub 2021 May 29.
Inherited and age-related retinal degeneration is the hallmark of a large group of heterogeneous diseases and is the main cause of untreatable blindness today. Genetic factors play a major pathogenic role in retinal degenerations for both monogenic diseases (such as retinitis pigmentosa) and complex diseases with established genetic risk factors (such as age-related macular degeneration). Progress in genotyping techniques and back of the eye imaging are completing our understanding of these diseases and their manifestations in patient populations suffering from retinal degenerations. It is clear that whatever the genetic cause, the majority of vision loss in retinal diseases results from the loss of photoreceptor function. The timing and circumstances surrounding the loss of photoreceptor function determine the adequate therapeutic approach to use for each patient. Among such approaches, gene therapy is rapidly becoming a therapeutic reality applicable in the clinic. This massive move from laboratory work towards clinical application has been propelled by the advances in our understanding of disease genetics and mechanisms, gene delivery vectors, gene editing systems, and compensatory strategies for loss of photoreceptor function. Here, we provide an overview of existing modalities of retinal gene therapy and their relevance based on the needs of patient populations suffering from inherited retinal degenerations.
遗传性和年龄相关性视网膜变性是一大组异质性疾病的标志，也是当今无法治疗的失明的主要原因。遗传因素在单基因疾病（如色素性视网膜炎）和具有既定遗传风险因素的复杂疾病（如年龄相关性黄斑变性）的视网膜变性中起主要致病作用。基因分型技术和眼底成像的进步完善了我们对这些疾病及其在患有视网膜变性的患者人群中的表现的认识。很明显，无论遗传原因如何，大多数视网膜疾病的视力丧失都是由于光感受器功能的丧失。光感受器功能丧失的时间和情况决定了每个患者应采用的适当治疗方法。在这些方法中，基因治疗正在迅速成为一种可应用于临床的治疗方法。这种从实验室工作到临床应用的大规模转变是由我们对疾病遗传学和机制、基因传递载体、基因编辑系统以及光感受器功能丧失的补偿策略的理解的进步推动的。在这里，我们根据遗传性视网膜变性患者群体的需求，概述了现有的视网膜基因治疗方式及其相关性。
